Abnormal Development - Developmental Origins of Health and Disease

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Introduction

Normal distribution curve on graph
Normal distribution curve (red)

Environmental derived abnormalities relate to maternal lifestyle, environment and nutrition and while some of these directly effect embryonic development, there is also growing evidence that some effects are more subtle and relate to later life health events.


This theory, now called "developmental origins of health and disease" (DOHAD or DOHaD) and also previously Fetal Origins Hypothesis, is based on the early statistical analysis carried out by David Barker (1938 - 2013) of low birth weight data collected in the early 1900's in the south east of England which he then compared with these same babies later health outcomes. The theory was therefore originally called the "Barker Hypothesis" and has recently been renamed as "fetal origins" or "programming". Several origins have been suggested including: fetal undernutrition, endocrine (increased cortisol exposure), genetic susceptibility and accelerated postnatal growth.


More recently, discussion has occurred relating to how the data is both collected and analyzed, suggesting perhaps a smaller effect than original research suggested (see Lucas reference). Statistical methodology aside, these studies long-term periods of accurate data collection and we may have to wait some time for this research to develop.


Some research has now shifted from birth weight emphasis to that of the early postnatal infant growth. (More? Postnatal - Growth Charts)


Abnormality Links: abnormal development | abnormal genetic | abnormal environmental | Unknown | teratogens | ectopic pregnancy | cardiovascular abnormalities | Coelomic Cavity | endocrine abnormalities | gastrointestinal abnormalities | genital abnormalities | head abnormalities | integumentary abnormalities | musculoskeletal abnormalities | limb abnormalities | neural abnormalities | neural crest abnormalities | renal abnormalities] | respiratory abnormalities | placenta abnormalities | hearing abnormalities | vision abnormalities | twinning | Developmental Origins of Health and Disease | ICD-11
Historic Embryology  
1915 Congenital Cardiac Disease | 1917 Frequency of Anomalies in Human Embryos | 1920 Hydatiform Degeneration Tubal Pregnancy | 1921 Anencephalic Embryo | 1921 Rat and Man | 1966 Congenital Malformations
| Birth-Weight

Some Recent Findings

  • DOHAD2017 10th anniversary World Congress in Rotterdam.
  • Delivery of a small for gestational age infant and greater maternal risk of ischemic heart disease[1] "Delivery of a small for gestational age (SGA) infant has been associated with increased maternal risk of ischemic heart disease (IHD). ...Risk of maternal IHD was evaluated in a population based cross-sectional study of 6,608 women with a prior live term birth who participated in the National Health and Nutrition Examination Survey (1999-2006), a probability sample of the U.S. population....Giving birth to a SGA infant is strongly and independently associated with IHD and a potential risk factor that precedes IHD by decades. A pregnancy that produces a SGA infant may induce long-term cardiovascular changes that increase risk for IHD." (Note this paper refers to a Maternal not Neonatal Risk).
  • Fetal origins of adult diabetes[2] "According to the fetal origin of adult diseases hypothesis, the intrauterine environment through developmental plasticity may permanently influence long-term health and disease. Therefore, intrauterine growth restriction (IUGR), due either to maternal, placental, or genetic factors, may permanently alter the endocrine-metabolic status of the fetus, driving an insulin resistance state that can promote survival at the short term but that facilitates the development of type 2 diabetes mellitus and metabolic syndrome in adult life, especially when the intrauterine nutrient restriction is followed by a postnatal obesogenic environment."
  • Perinatal Risk Factors for Diabetes in Later Life[3] "Low birth weight is consistently associated with an increased risk of non-insulin dependent diabetes mellitus in adulthood, but the individual contributions from poor fetal growth and preterm birth are not known. ....Our results suggest that the association between low birth weight and diabetes is due to factors associated with both poor fetal growth and short gestational age."
More recent papers  
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This table shows an automated computer PubMed search using the listed sub-heading term.

  • Therefore the list of references do not reflect any editorial selection of material based on content or relevance.
  • References appear in this list based upon the date of the actual page viewing.

References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.

Links: References | Discussion Page | Pubmed Most Recent | Journal Searches


Search term: Developmental Origins of Health and Disease

Ramkripa Raghavan, Barry Zuckerman, Xiumei Hong, Guoying Wang, Yuelong Ji, David Paige, Jessica DiBari, Cuilin Zhang, M Daniele Fallin, Xiaobin Wang Fetal and Infancy Growth Pattern, Cord and Early Childhood Plasma Leptin, and Development of Autism Spectrum Disorder in the Boston Birth Cohort. Autism Res: 2018; PubMed 30248249

Carol L Wagner, Bruce W Hollis The Implications of Vitamin D Status During Pregnancy on Mother and her Developing Child. Front Endocrinol (Lausanne): 2018, 9;500 PubMed 30233496

Tamara J Varcoe Timing is everything: maternal circadian rhythms and the developmental origins of health and disease. J. Physiol. (Lond.): 2018; PubMed 30204232

Older papers  
  • Persistent epigenetic differences associated with prenatal exposure to famine in humans[4] "Here we show that individuals who were prenatally exposed to famine during the Dutch Hunger Winter in 1944-45 had, 6 decades later, less DNA methylation of the imprinted IGF2 gene compared with their unexposed, same-sex siblings. The association was specific for periconceptional exposure, reinforcing that very early mammalian development is a crucial period for establishing and maintaining epigenetic marks." (More? see also Molecular Development - Epigenetics)
  • The fetal origins hypothesis—10 years on (2005)[5] "In 1995 David Barker wrote: “The fetal origins hypothesis states that fetal undernutrition in middle to late gestation, which leads to disproportionate fetal growth, programmes later coronary heart disease.”1 Now, 10 years later, the importance of events before birth for lifetime health has been confirmed in many populations."

Barker Hypothesis

David Barker (1938 - 2013)

There were some key papers by David Barker that initially studied UK birth weight data that gave rise to this area of research.[6][7][8]

“The fetal origins hypothesis states that fetal undernutrition in middle to late gestation, which leads to disproportionate fetal growth, programmes later coronary heart disease.”


See also Fetal origins of adult disease-the hypothesis revisited.[9]

  • The hypothesis that adult disease has fetal origins is plausible, but much supportive evidence is flawed by incomplete and incorrect statistical interpretation.
  • When size in early life is related to later health outcomes only after adjustment for current size, it is probably the change in size between these points (postnatal centile crossing) rather than fetal biology that is implicated.
  • Even when birth size is directly related to later outcome, some studies fail to explore whether this is partly or wholly explained by postnatal rather that prenatal factors.
  • These considerations are critical to understanding the biology and timing of "programming," the direction of future research, and future public health interventions.

David Barker (1938 - 2013)

Professor David Barker FRS, born 29 June 1938; died 27 August 2013.


"David Barker was one of the most influential clinical epidemiologists of our time. He challenged the idea that chronic disorders such as diabetes and cardiovascular disease are explained only by bad genes and unhealthy adult lifestyles. His 'Barker hypothesis' proposed that the fetal environment and early infant health permanently programme the body's metabolism and growth, and thus determine the pathologies of old age. Initially controversial, his ideas triggered an explosion of research worldwide into the relationship between early development and adult disease."[10]
"David Barker received the prestigious Richard Doll Prize in 2011 given by the International Epidemiology Association (IEA). This prize is given to a person who deserved to be a candidate for the Nobel Prize but would probably not be accepted by the Nobel Committee because of the way epidemiologic research is structured and conducted. In epidemiology we can seldom point towards a specific article or even a few articles or a single person who, by himself alone, changes the way we think."[11]


Links: memorial service

Fetal Growth Articles

Fetal growth.[12] "Recent epidemiological and experimental studies show that abnormal fetal growth can lead to serious complications, including stillbirth, perinatal morbidity and disorders extending well beyond the neonatal period. It is now clear that the intrauterine milieu is as important as genetic endowment in shaping the future health of the conceptus. Maternal characteristics such as weight, height, parity and ethnic group need to be adjusted for, and pathological factors such as smoking excluded, to establish appropriate standards and improve the distinction between what is normal and abnormal. Currently, the aetiology of growth restriction is not well understood and preventative measures are ineffective. Elective delivery remains the principal management option, which emphasizes the need for better screening techniques for the timely detection of intrauterine growth failure."

Fetal growth and long-term consequences in animal models of growth retardation.[13] "Perturbations of the maternal environment involve an abnormal intrauterine milieu for the developing fetus. The altered fuel supply (depends on substrate availability, placental transport of nutrients and uteroplacental blood flow) from mother to fetus induces alterations in the development of the fetal endocrine pancreas and adaptations of the fetal metabolism to the altered intrauterine environment, resulting in intrauterine growth retardation. The alterations induced by maternal diabetes or maternal malnutrition (protein-calorie or protein deprivation) have consequences for the offspring, persisting into adulthood and into the next generation."

Diabetes

Fetal origins of adult diabetes[2] "According to the fetal origin of adult diseases hypothesis, the intrauterine environment through developmental plasticity may permanently influence long-term health and disease. Therefore, intrauterine growth restriction (IUGR), due either to maternal, placental, or genetic factors, may permanently alter the endocrine-metabolic status of the fetus, driving an insulin resistance state that can promote survival at the short term but that facilitates the development of type 2 diabetes mellitus and metabolic syndrome in adult life, especially when the intrauterine nutrient restriction is followed by a postnatal obesogenic environment."

Perinatal Risk Factors for Diabetes in Later Life[3] "Low birth weight is consistently associated with an increased risk of non-insulin dependent diabetes mellitus in adulthood, but the individual contributions from poor fetal growth and preterm birth are not known. ....Our results suggest that the association between low birth weight and diabetes is due to factors associated with both poor fetal growth and short gestational age."

Renal

The Brenner hypothesis is a clinical hypothesis that states, individuals with a congenital reduction in nephron number have a much greater likelihood of developing adult hypertension and subsequent renal failure.[14] The hypothesis was developed in the 1980's by Barry Brenner a neurologist and researcher at the Brigham and Women's Hospital. This "congenital reduction" also fits with this DOHAD hypothesis.


Links: Renal System Development | Barry Brenner

Cardiovascular

Neural Effects

The hypothesis proposes influences cause permanent changes in embryo/fetus, low birth weight, predisposition to chronic disease in adult life. Malnutrition in utero affects brain development, "low birth weight" or intrauterine growth restricted babies fare less well on measures of mental development in later life studies compared low birth weight babies (<2500 g) with controls, show impairment in neuro developmental tests up to age 11.

Intelligence is a combination of genetic and environmental influences (relative contributions of which are not yet established) and may vary over lifespan.

(Modified Text from[15] Note the commment made by Emeritus Professor P Pharaoh "One caveat that should be borne in mind, concerns the tests that are used to assess cognitive function. What do these tests actually measure? Ideally they measure innate mental ability, whatever that is, at a point in time.")

In contrast, a recent study of only postnatal growth (to 3 years of age) identified "Slower infant weight gain was not associated with poorer neurodevelopmental outcomes in healthy, term-born 3-year-old children."[16]

NCBI Bookshelf

Resources available from online textbooks freely available at National Library of Medicine (USA), National Center for Biotechnology Information.

Health Services/Technology Assessment Text (HSTAT)

Evidence table 3. Studies Evaluating Association of LBW and Cerebral Palsy and Neurological Outcomes Part I

Evidence table 5B. Studies Evaluating Association of LBW of Audiology Outcomes Part II

Birth Terms

  • Premature infant - An infant born before 37 weeks of estimated gestational age
  • Low birth weight - Birth weight < 2,500 g (5 lb, 8 oz)
  • Very low birth weight - Birth weight < 1,500 g (3 lb, 5 oz)
  • Extremely low birth weight - Birth weight < 1,000 g (2 lb, 3 oz)

References

  1. Bukowski R, Davis KE & Wilson PW. (2012). Delivery of a small for gestational age infant and greater maternal risk of ischemic heart disease. PLoS ONE , 7, e33047. PMID: 22431995 DOI.
  2. 2.0 2.1 Kanaka-Gantenbein C. (2010). Fetal origins of adult diabetes. Ann. N. Y. Acad. Sci. , 1205, 99-105. PMID: 20840260 DOI.
  3. 3.0 3.1 Kaijser M, Bonamy AK, Akre O, Cnattingius S, Granath F, Norman M & Ekbom A. (2009). Perinatal risk factors for diabetes in later life. Diabetes , 58, 523-6. PMID: 19066311 DOI.
  4. Heijmans BT, Tobi EW, Stein AD, Putter H, Blauw GJ, Susser ES, Slagboom PE & Lumey LH. (2008). Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc. Natl. Acad. Sci. U.S.A. , 105, 17046-9. PMID: 18955703 DOI.
  5. Eriksson JG. (2005). The fetal origins hypothesis--10 years on. BMJ , 330, 1096-7. PMID: 15891207 DOI.
  6. Barker DJ. (1990). The fetal and infant origins of adult disease. BMJ , 301, 1111. PMID: 2252919
  7. Barker DJ & Martyn CN. (1992). The maternal and fetal origins of cardiovascular disease. J Epidemiol Community Health , 46, 8-11. PMID: 1573367
  8. Barker DJ. (1997). Fetal nutrition and cardiovascular disease in later life. Br. Med. Bull. , 53, 96-108. PMID: 9158287
  9. Lucas A, Fewtrell MS & Cole TJ. (1999). Fetal origins of adult disease-the hypothesis revisited. BMJ , 319, 245-9. PMID: 10417093
  10. Cooper C. (2013). David Barker (1938-2013). Nature , 502, 304. PMID: 24132283 DOI.
  11. Olsen J. (2014). David Barker (1938-2013)--a giant in reproductive epidemiology. Acta Obstet Gynecol Scand , 93, 1077-80. PMID: 24628330 DOI.
  12. Mongelli M & Gardosi J. (2000). Fetal growth. Curr. Opin. Obstet. Gynecol. , 12, 111-5. PMID: 10813572
  13. Holemans K, Aerts L & Van Assche FA. (1998). Fetal growth and long-term consequences in animal models of growth retardation. Eur. J. Obstet. Gynecol. Reprod. Biol. , 81, 149-56. PMID: 9989859
  14. Brenner BM, Garcia DL & Anderson S. (1988). Glomeruli and blood pressure. Less of one, more the other?. Am. J. Hypertens. , 1, 335-47. PMID: 3063284
  15. Shenkin SD, Starr JM, Pattie A, Rush MA, Whalley LJ & Deary IJ. (2001). Birth weight and cognitive function at age 11 years: the Scottish Mental Survey 1932. Arch. Dis. Child. , 85, 189-96. PMID: 11517097
  16. Belfort MB, Rifas-Shiman SL, Rich-Edwards JW, Kleinman KP, Oken E & Gillman MW. (2008). Infant growth and child cognition at 3 years of age. Pediatrics , 122, e689-95. PMID: 18762504 DOI.

Journal

  • Journal of Developmental Origins of Health and Disease JDOHaD publishes leading research in the field of developmental origins of health and disease (DOHaD), focusing on how the environment during early animal and human development, and interactions between environmental and genetic factors, influence health in later life and risk of disease. [jour PubMed listing]

Book Developmental origins of health and disease Reviewed by R L Boon Edited by Peter Gluckman, Mark Hanson. Published by Cambridge University Press, Cambridge, 2006, £85.00, pp 519. ISBN 0-521-84743-5

Reviews

Calkins K & Devaskar SU. (2011). Fetal origins of adult disease. Curr Probl Pediatr Adolesc Health Care , 41, 158-76. PMID: 21684471 DOI.

Geelhoed JJ & Jaddoe VW. (2010). Early influences on cardiovascular and renal development. Eur. J. Epidemiol. , 25, 677-92. PMID: 20872047 DOI.

Kanaka-Gantenbein C. (2010). Fetal origins of adult diabetes. Ann. N. Y. Acad. Sci. , 1205, 99-105. PMID: 20840260 DOI.

Cota BM & Allen PJ. (2010). The developmental origins of health and disease hypothesis. Pediatr Nurs , 36, 157-67. PMID: 20687308

Tamashiro KL & Moran TH. (2010). Perinatal environment and its influences on metabolic programming of offspring. Physiol. Behav. , 100, 560-6. PMID: 20394764 DOI.

Langley-Evans SC & McMullen S. (2010). Developmental origins of adult disease. Med Princ Pract , 19, 87-98. PMID: 20134170 DOI.

Wadhwa PD, Buss C, Entringer S & Swanson JM. (2009). Developmental origins of health and disease: brief history of the approach and current focus on epigenetic mechanisms. Semin. Reprod. Med. , 27, 358-68. PMID: 19711246 DOI.

Articles

Mook-Kanamori DO, Steegers EA, Eilers PH, Raat H, Hofman A & Jaddoe VW. (2010). Risk factors and outcomes associated with first-trimester fetal growth restriction. JAMA , 303, 527-34. PMID: 20145229 DOI.

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Cite this page: Hill, M.A. (2018, September 26) Embryology Abnormal Development - Developmental Origins of Health and Disease. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Abnormal_Development_-_Developmental_Origins_of_Health_and_Disease

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